This invention relates to pharmaceutical compositions which have activity as anti-cancer agents against carcinoma and to methods for the treatment of carcinoma in patients.
It has been known for some time that the levels of ascorbic acid (vitamin C) are often low in cancer patients, which may be due to increased utilization of ascorbate by tumour cells. It has therefore been suggested that ascorbic acid might be a useful anti-cancer therapeutic agent in anti-cancer therapy. As reviewed by Cameron et al (Cancer Res., 39:663-681, 1979) some clinical trials have shown significant increases in survival times of cancer patients receiving ascorbate. However, to date, ascorbic acid has not found wide use as an anti-cancer agent.
More recently, it has been proposed to form adducts of ascorbic acid with other compounds in order to provide novel anti-cancer agents. Thus, for example, Elvin et al have reported (Eur. J. Cancer Clin. Oncol, 17(7), 1981, 759-65) that adducts of ascorbic acid with aldehydes such as methylglyoxal and acetylacrolein inhibit the growth of the Ehrlich ascites carcinoma in mice. Again, the use of ethers of, inter alia, ascorbic acid, and ketals and acetals thereof, as angiogenesis inhibiting agents is proposed in EP-A-0086544. Angiogenesis refers to the process of new blood vessel development, the proliferation of new blood vessels being involved in e.g. tumour growth.
More recently still, it has been disclosed in EP-A-0148094 that 5,6-O-benzylidene-L-ascorbic acid, and metal salts thereof, exhibit anti-cancer properties. This compound may be prepared by reacting L-ascorbic acid with either benzaldehyde in the presence of zinc chloride or with .alpha.,.alpha.-dimethoxytoluene, for example, and has the chemical structure shown below: ##STR1##